P713: REAL-WORLD MANAGEMENT OF PATIENTS WITH CHRONIC MYELOID LEUKAEMIA (CML): FIRST ANALYSIS FROM THE UK NATIONAL REGISTRY FOR CML
Authors: G. Nesr, R. Szydlo, B. Braithwaite, S. Frackelton, P. Mathew, M. Hashmi, F. Fernando, A. Innes, S. Claudiani, A. Khan, A. Rao, L. Foroni, D. Milojkovic, J. F. Apperley, R. E. Clark
Journal: HemaSphere (2022)

Background: Analysing data emerging from population based cancer registries (PBCR) informs current practice. The UK National Registry for chronic myeloid leukaemia (CML) patients (ptn) is a web-based PBCR, initially established as a regional registry in 2010, then expanded nationally in 2015. Aims: To understand real world management of UK CML ptn. Methods: The registry utilizes an online interface to capture baseline and yearly follow up data from contributing centres (CC). Data are securely transferred using the N3 backbone of the NHS network. Ptn are consented for enrolment at their respective centres. A “treatment episode” is defined as the duration during which a ptn received a specific tyrosine kinase inhibitor (TKI). The 2013 version of the ELN guidelines was used to define treatment milestones. For each milestone timepoint, treatment switches were counted if they occurred before the next milestone. Results: Demographic and baseline disease characteristics data were available for 748 ptn from 43 CC (Figure 1). Of those, 79%, 75% and 94% had available karyotypes, FISH for BCR-ABL1, and RT-PCR for BCR-ABL1, respectively, at diagnosis and/or follow up. Follow up and treatment data were available for 570 and 534 ptn, respectively. Median follow up duration was 4.7 years (range: 0.1-23.7). Median age at diagnosis was 53.3 years (range: 14.6-95.1) and 53% were males. Karyotype and RT- PCR for BCR ABL1 at diagnosis were available for >75% of ptn in 40% of CC. Molecular monitoring data were available for 540 ptn: 342 (63%) had a median testing frequency of ≤ 3 months, 167 (31%) between 3-6 months, 20 (4%) between 6-12 months, and 11 (2%) of > 12 months. Imatinib (IM), nilotinib (NIL), dasatinib (DAS), bosutinib and ponatinib were prescribed as 1st or subsequent line therapy in 46%, 23%, 21%, 14%, and 7% of the treatment episodes, respectively. IM remained the most frequent 1st-line treatment after NICE approval of 2GTKI in newly diagnosed ptn. The choice of 1st line TKI (IM vs 2G) was not influenced by the Sokal, Euro, EUTOS or ELTS scores. Of ptn started on 1st line IM, NIL, and DAS; 94%, 63% and 100% received the licensed doses (400 mg OD, 300 mg BD, and 100 mg OD), respectively. Optimal responses at 3,6 and 12 months were achieved in 73%, 63%, and 51% of pts. Failure at 3 months was not evaluable as the registry did not capture sequential FBCs. Of those with a suboptimal response at 3 months, 15% changed treatment. At 6 months 28% and 50% of ptn with suboptimal and failure responses, respectively, switched their TKI. At 12 months, 10% and 28% of ptn in the suboptimal and failure categories changed TKI. Between 1-6 treatment switches, for failure and/or intolerance, occurred in 46% of ptn. Treatment switches on IM were more common for resistance than intolerance and vice versa for 2G and 3G TKI. Of all ptn who switched TKI, 40% underwent a further TKI switch. Kinase domain mutation analysis was requested in 36% and 33% of ptn resistant to their TKI at 6 and 12 months, respectively. Five-year overall survival (OS) probability was 93% for CP-CML ptn. Ptn achieving CCyR had a significantly higher OS probability than those who did not (p<0.001 by log rank test). However, differences in OS probability were not statistically significant for ptn attaining deeper responses (p<0.5 for MR3, p<0.076 for MR4, p<0.141 for MR4.5, and p<0.084 for MR5). Image:Summary/Conclusion: Our results highlight the lack of conformance to the current guidelines in various aspects of CML management, the excellent OS survival achievable with currently available TKIs and the importance of achieving CCyR for better OS.